Findings to date: 1) a significant improvement in measures of depression and libido after DHEA administration in men and women with midlife-related major and minor depression; 2) neither short term (six week) nor long term (six months-one year) administration of DHEA significantly altered measures of bone metabolism or bone density; 3) a significant improvement in measures of depression was seen after six weeks of either estradiol or the SERM raloxifene, but not after either placebo or phytoestrogen in women with perimenopausal depression who have completed a double-blind, placebo-controlled, parallel design trial; 4) raloxifene also was associated with an increase in plasma estradiol levels; 5) women with a past perimenopausal depression but not those without such a history experience mood symptoms during short term estradiol withdrawal under blinded, placebo-controlled conditions; 6) a higher than expected co-occurrence of prospectively confirmed premenstrual dysphoria and perimenopausal depression, 7) the clustering of the onset of perimenopausal depressions during the late menopause transition (as defined by STRAW), and 8) the absence of a cuasal relationship between hot flushes and depression in perimenopausal women.[unreadable] [unreadable] In collaboration with NICHD we have observed that women with Turner Syndrome have significantly higher scores on measures of shyness, depression and anxiety than asymptomatic controls but their scores do not differ from those in women with premature ovarian insufficiency (POI). Finally, women with POI report an increased lifetime frequency of major depression compared with community samples of women (i.e., 69.5% versus 20%, respectively), and the majority of these depressive episodes occurred after the onset of menstrual cycle irregularity but before the final menstrual period and the diagnosis of POI.